Adjustable glaucoma implant

ABSTRACT

Methods and devices for adjusting or configuring the flow rate of an intraocular shunt are provided whereby hypotony can be avoided by increasing the flow rate through the device. In some embodiments, the device is a shunt that can have a first flow that can be modified to a second flow by modifying the shunt, such as by cutting the shunt. Additionally, one or more dissolvable portions can be present to provide an initial flow restriction and subsequent increase in flow over time.

BACKGROUND

Glaucoma is a disease of the eye that affects millions of people.Glaucoma is associated with an increase in intraocular pressureresulting either from a failure of a drainage system of an eye toadequately remove aqueous humor from an anterior chamber of the eye oroverproduction of aqueous humor by a ciliary body in the eye. Build-upof aqueous humor and resulting intraocular pressure may result inirreversible damage to the optic nerve and the retina, which may lead toirreversible retinal damage and blindness.

Glaucoma may be treated in a number of different ways. One manner oftreatment involves delivery of drugs such as beta-blockers orprostaglandins to the eye to either reduce production of aqueous humoror increase flow of aqueous humor from an anterior chamber of the eye.Glaucoma filtration surgery is a surgical procedure typically used totreat glaucoma. The procedure involves placing a shunt in the eye torelieve intraocular pressure by creating a pathway for draining aqueoushumor from the anterior chamber of the eye. The shunt is typicallypositioned in the eye such that it creates a drainage pathway betweenthe anterior chamber of the eye and a region of lower pressure. Suchfluid flow pathways allow for aqueous humor to exit the anteriorchamber.

SUMMARY

The importance of lowering intraocular pressure (IOP) in delayingglaucomatous progression has been well documented. When drug therapyfails, or is not tolerated, surgical intervention is warranted. Thereare various surgical filtration methods for lowering intraocularpressure by creating a fluid flow-path between the anterior chamber andthe subconjunctival tissue. In one particular method, an intraocularshunt is implanted by directing a needle which holds the shunt throughthe cornea, across the anterior chamber, and through the trabecularmeshwork and sclera, and into the subconjunctival space. See, forexample, U.S. Pat. No. 6,544,249, U.S. Patent Application PublicationNo. 2008/0108933, and U.S. Pat. No. 6,007,511, the entireties of whichare incorporated herein by reference.

However, existing implantable shunts may not effectively regulate fluidflow from the anterior chamber. Fluid flow through a traditional shuntis passive, from the anterior chamber to a drainage structure of theeye. If fluid flows from the anterior chamber at a rate greater than itcan be produced in the anterior chamber, the surgery can result in anundesirably low intraocular pressure in the anterior chamber of the eye.This condition is known as hypotony. Hypotony occurs when theintraocular pressure is generally less than about 6 mmHg. Risksassociated with low intraocular pressure and hypotony include blurredvision, collapse of the anterior chamber, and potentially significantdamage to the eye. Such risks could require additional surgicalintervention to repair. However, if fluid flow from the eye is not greatenough, pressure in the anterior chamber will not be relieved, anddamage to the optic nerve and the retina may still occur.

Accordingly, some embodiments disclosed herein provide intraocularimplants or shunts for draining fluid from an anterior chamber of an eyeand methods of use that enable a clinician to selectively adjust orconfigure the flow rate or flow parameters of an intraocular shunt inorder to avoid hypotony while ensuring that adequate pressure relief isprovided.

For example, an intraocular implant or shunt can be provided that isconfigured to conduct fluid at a first nonzero flow that can be modifiedto a second flow, when the implant is in an eye, by removing part of theimplant.

Some implants can be configured to have a first flow that can be changedto a second flow by shortening the length of the implant.

Some implants can be configured to have a first flow that can be changedto a second flow by removing a restrictive section thereof.

In some embodiments, the first flow can be less than the second flowthrough the implant. Thus, modification, shortening, or removal of asection thereof can increase the flow through the implant.

An eye implant can be provided that conducts fluid at a first nonzeroflow rate, modifiable to a second flow rate, when the implant is in aneye, by removing a removable part of the implant residing in theanterior chamber.

The implant can comprise a wall defining a lumen, and the wall can havea variable inner profile. The implant can also comprise a partiallyrestrictive end. For example, the implant can a gelatin tube that isinserted into the lumen, and the gelatin tube can have an inner profilesmaller than an inner profile of the implant lumen.

A longitudinal length of some implants can be shortened to modify thefirst flow. For example, the first flow rate can be increased to thesecond flow rate when the implant is cut at a first point along theimplant. Further, the first flow rate can be increased to a third flowrate when the implant is cut at a second point along the implant.

Some implants or shunts can comprise a hollow body with a clear-through,unobstructive, or unrestrictive main section and a partially obstructiveor flow-limiting restrictive section. The first flow of the shunt can bemodifiable to the second flow by modifying, shortening, or removing partof the main section and/or the partially restrictive section.

The main section can have an inlet, an outlet, and a wall defining alumen extending between the inlet and outlet. The inlet can beconfigured to receive fluid from the anterior chamber. The main sectioncan comprise a wall defining a lumen. The wall can define a firstcross-sectional area or profile and can be configured to direct thefluid from the anterior chamber through the inlet toward the outlet suchthat, when positioned in the eye, fluid is released through the outletat a location having lower pressure than the anterior chamber. Asdiscussed herein, the location of lower pressure can be, for example,the intra-Tenon space, the subconjunctival space, the episcleral vein,the suprachoroidal space, or Schlemm's canal.

The partially restrictive section can be in fluid communication with themain section. The partially restrictive section can have a second flowcross-sectional area or profile that is less that the firstcross-sectional area or profile.

For example, the partially restrictive section can comprise a gelatintube. The gelatin tube can be inserted into a lumen of the main sectionand comprise a wall defining a lumen with a smaller cross-sectional areaor profile than the main section cross-sectional area or profile.

The shunt can be configured such that the first flow cross-sectionalarea is generally circular in shape. Further, the partially restrictivesection of the shunt can be formed of a separate material from the mainsection. The partially restrictive section can be dissolvable. Forexample, the partially restrictive section has a dissolution rate thatis different than a dissolution rate of the shunt.

In some embodiments, the shunt can be configured such that the partiallyrestrictive section comprises first and second portions. For example,the first and second portions can be axially spaced apart from eachother. The first and second portions can be concentrically layeredwithin the lumen. The first and second portions can also be positionedat opposing ends of the main section. The first and second portions canbe dissolvable. For example, the first portion can have a firstdissolution rate, and the second portion can have a second dissolutionrate that is different from the first dissolution rate.

Additionally, the shunt can be configured such that at least a portionof the body comprises a drug. For example, the partially restrictivesection can comprise a drug. Further, the partially restrictive sectioncan comprise a gelatin. The main section can comprise a cross-linkedgelatin. Further, the partially restrictive section can comprise across-linked gelatin that is cross-linked to a different degree than thecross-linked gelatin of the main section.

In some embodiments, various methods for implanting an intraocular shuntare provided. A hollow shaft, configured to hold the intraocular shunt,can be inserted into the eye. Thereafter, the shunt can be deployed fromthe hollow shaft such that the shunt extends between an anterior chamberof the eye to a location of lower pressure of the eye. Once the shunt isin proper position, the hollow shaft can be withdrawn from the eye. Asdiscussed herein, in some embodiments, the shunt can have one or moreremovable portions and/or one or more dissolvable sections. All or atleast a portion of the shunt can be dissolvable. Further, in someembodiments, the one or more removable portions can be dissolvable.

In some embodiments, a method of treating glaucoma is provided in whichan intraocular shunt is placed in an eye, in a first medical procedure.In the first procedure, the shunt can be placed to extend from ananterior chamber of the eye to a location of lower pressure of the eye.The shunt can be configured to provide a first nonzero flow rate.Thereafter, the eye can heal from the first medical procedure.Subsequent to the healing of the eye, in a second medical procedure, theintraocular shunt can be cut to provide a second flow rate, greater thanthe first flow rate.

The intraocular pressure of the eye can be measured in performing themethod or performing checkups. After the intraocular pressure has beenmeasured and reaches a threshold level, the step of cutting theintraocular shunt can be performed. For example, the step of cutting canbe performed when the threshold level is greater than about 20 mmHg.

In some methods, in a first medical procedure as noted above, anintraocular shunt can be placed in an eye to extend from an anteriorchamber of the eye to a location of lower pressure of the eye. The shuntcan provide a first nonzero flow rate. However, a second medicalprocedure can be performed, after a threshold period of time has passedsince the first medical procedure, in which the intraocular shunt is cutto provide a second flow rate, greater than the first flow rate.

For example, the step of cutting the intraocular shunt can be performedafter a period of from about one week to about three months. In somecases, the step of cutting the intraocular shunt can be performed afterabout six (6) weeks. Further, such procedures can also be performedafter permitting the eye to heal from the first medical procedure.

Methods are also provided of adjusting the flow rate of an intraocularshunt implanted in an eye. For example, a clinician can determine theposition of a shunt, which has been placed in the eye to extend betweenan anterior chamber of the eye and a location of lower pressure of theeye. When the shunt position is determined, the clinician can thereaftercut a first portion of the shunt, thereby increasing flow through theshunt.

In some methods, prior to cutting the shunt, for example, the cliniciancan determine an intraocular pressure of the eye and determine a targetpressure drop necessary to achieve normal intraocular pressure. Once thetarget pressure drop is determined, the clinician can determine a targetlongitudinal length of the first portion based on the target pressuredrop. Accordingly, when the first portion of the shunt is cut, it can becut at the target length.

After the first portion is cut, the first portion can be separated fromthe shunt. For example, the method can further comprise removing thefirst portion from the eye.

Additionally, the shunt can comprise a tapered lumen or tapering wall.The shunt can be cut at a specific point corresponding to a walldimension along the taper thereof. Thus, multiple cut locations can beavailable in order to allow the clinician several options for targetlengths or target flow rates.

The shunt can have a partially restrictive section and a main section.The partially restrictive section can have a cross-sectional area lessthan a cross-sectional area of the main section. The first portion canhave a longitudinal length is less than a longitudinal length of thepartially restrictive section.

In some embodiments, the shunt can be modified, e.g., cut, trimmed,spliced, punctured, split, etc., to adjust the flow rate of the shunt. Aportion of main section can be separated from the shunt to adjust theflow. Further, when present, the partially restrictive section (in itsentirety or only a fragment or section thereof) can be separated fromthe shunt such that flow rate of the shunt is modified, such as byincreasing.

The method can comprise inserting into the eye a hollow shaft configuredto hold the intraocular shunt. Thereafter, the shunt can be deployedfrom the hollow shaft such that the shunt forms a passage from theanterior chamber of the eye to a location of lower pressure of the eye.In some embodiments, the shunt can have a partially obstructive orflow-limiting restrictive section and an unobstructive or unrestrictivemain section. The shunt can have a first flow rate or flow value withthe partially restrictive section present. The method can compriseremoving a portion of the partially restrictive section.

In some embodiments, a method of adjusting the flow rate of anintraocular shunt implanted in an eye can comprise determining aposition of the shunt in the eye extending from (i) an anterior chamberof the eye to (ii) a location of lower pressure of the eye. Thepartially restrictive section can be dimensioned to have a first innercross-sectional dimension. The main section can be dimensioned to have asecond, larger inner cross-sectional dimension, different than the firstdimension, through the shunt.

The first dimension can be less than the second dimension. The first andsecond dimensions can relate to a flow value or flow rate for therespective section. In some embodiments, the shunt or first dimensioncan comprise a ratio of an inner diameter and an axial length of themain section and an inner diameter and an axial length of the partiallyrestrictive section. Further, after a fragment or section of the shuntis removed from the shunt, the shunt or second dimension can comprise aratio of an inner diameter and an axial length of the main section andan inner diameter and an axial length of any remaining portion of thepartially restrictive section. In some embodiments, a fragment orsection of the partially restrictive section and/or a fragment orsection of the main section can be separated from the shunt, therebyincreasing the flow rate through the shunt. For example, in someembodiments, when the fragment or section of the partially restrictivesection is separated from the shunt, the flow rate can increase.

The flow rate can increase from a first flow rate to a second flow rate.When the restrictive section is modified, the first flow rate is thecollective flow rate through the restrictive and main sections and thesecond flow rate is the flow rate through the main section and anyremaining portion of the restrictive section.

The shunt can be configured with various ranges of dimensions. Forexample, the total shunt length can be from about 4 mm to about 12 mm.In some embodiments, the total shunt length can be from about 5 mm toabout 10 mm. In some embodiments, the total shunt length can be about 6mm.

Further, the inner diameter of the main section can be from about 80 μmto about 300 μm. In some embodiments, the inner diameter of the mainsection can be from about 120 μm to about 200 μm. In some embodiments,the inner diameter of the main section can be about 150 μm.

The length of the partially restrictive section can be from about 0.2 mmto about 6 mm. In some embodiments, the partially restrictive sectionlength can be from about 1 mm to about 4 mm. In some embodiments, thepartially restrictive section length can be about 2 mm.

The inner diameter of the partially restrictive section can be fromabout 10 μm to about 70 μm. In some embodiments, the partiallyrestrictive section inner diameter can be from about 25 μm to about 55μm. In some embodiments, the partially restrictive section innerdiameter can be about 40 μm.

The method can be performed such that separating the fragment or sectionof the partially restrictive section comprises removing an end portionof the shunt. The end portion of the shunt can be configured such thatthe wall thereof defines a smaller lumen relative to the main section.Further, separating the fragment or section of the partially restrictivesection can comprise cutting the shunt using a mechanical device.Additionally, separating the fragment or section of the partiallyrestrictive section can comprise cutting the shunt using a needle.Furthermore, separating the fragment or section of the partiallyrestrictive section can comprise cutting the shunt using a cutting tool.For example, the cutting tool can comprise a pivot mechanism. Finally,other mechanisms or tools can be used to adjust the size orconfiguration of the shunt. For example, a laser can be used such thatseparating the fragment or section of the partially restrictive sectioncomprises cutting the shunt using a laser.

The partially restrictive section can be positioned in a subconjunctivalspace. Alternatively, the partially restrictive section can bepositioned in the anterior chamber of the eye.

In some embodiments, after the fragment or section of the partiallyrestrictive section has been separated from the shunt, the method canalso comprise removing the fragment or section of the partiallyrestrictive section. However, after the fragment or section of thepartially restrictive section has been separated from the shunt, thefragment or section of the partially restrictive section can be left inthe eye. For example, leaving the fragment or section of the partiallyrestrictive section in the eye can comprise leaving the fragment orsection of the partially restrictive section in the subconjunctivalspace.

Further, the fragment or section that is separated from the shunt may beless than the entirety of the partially restrictive section. Forexample, separating the fragment or section of the partially restrictivesection can comprise removing a first portion of the partiallyrestrictive section from the shunt and leaving a second portion of thepartially restrictive section attached to the shunt.

In some embodiments, an intraocular shunt that has an adjustable orvariable flow rate can be deployed into the eye. For example, the shuntcan have a partially restrictive dissolvable section and a main section.In some embodiments, the dissolvable section can define an aperture orlumen to conduct fluid therethrough. The shunt can have a first nonzeroflow rate through the dissolvable section.

The method can be performed such that deploying the shunt comprisespositioning the dissolvable section in the location of lower pressure.For example, the dissolvable section can be positioned in asubconjunctival space. Alternatively, however, the dissolvable sectioncan be positioned in the anterior chamber of the eye.

The dissolvable section can comprise a dissolvable plug having adissolution rate that is different than a dissolution rate of the mainsection. For example, the dissolution rate of the dissolvable plug canbe a nonzero number higher than the dissolution rate of the mainsection, which can be zero or a nonzero number.

The dissolvable section can also comprise first and second dissolvablesections. For example, the first and second dissolvable sections canhave different dissolution rates. Further, the first and seconddissolvable sections can be axially spaced apart from each other.Alternatively, the first and second dissolvable sections can beconcentrically layered within a lumen of the shunt.

As noted above, when a shunt having a dissolvable section is used, themethod can include the steps of determining the position of the shunt inthe eye extending from (i) the anterior chamber of the eye to (ii) thelocation of lower pressure of the eye; and separating a shunt fragmentof the dissolvable section from the shunt such that the shunt has asecond flow rate higher than the first flow rate.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide furtherunderstanding of the subject technology and are incorporated in andconstitute a part of this specification, illustrate aspects of thedisclosure and together with the description serve to explain theprinciples of the subject technology.

FIG. 1 is a partial cross-sectional diagram of an eye, illustrating abintern insertion of a deployment device, according to some embodiments.

FIG. 2 illustrates a schematic placement of an intraocular shunt withinintra-tenon space, according to some embodiments.

FIG. 3 illustrates a cross-sectional view of an intraocular shunt,according to some embodiments.

FIGS. 4-7 illustrate cross-sectional views of an end of an intraocularshunt of FIG. 3, according to some embodiments.

FIG. 8 illustrates placement of an intraocular shunt with a partialcross-sectional view of a partially restrictive section disposed in ananterior chamber of the eye, according to some embodiments.

FIG. 9 illustrates the severance of a portion of the partiallyrestrictive section of the shunt illustrated in FIG. 8, according tosome embodiments.

FIG. 10 illustrates placement of an intraocular shunt wherein apartially restrictive section is disposed in subconjunctival space,according to some embodiments.

FIG. 11 illustrates the severance of a portion of the partiallyrestrictive section of a shunt, oriented as illustrated in FIG. 10,according to some embodiments.

FIG. 12 illustrates the severance of a portion of the partiallyrestrictive section of a shunt, oriented as illustrated in FIG. 8, usinga laser, according to some embodiments.

FIG. 13 illustrates the severance of a portion of the partiallyrestrictive section of a shunt, oriented as illustrated in FIG. 10,using a laser, according to some embodiments.

FIG. 14 illustrates the severance of a portion of the partiallyrestrictive section of a shunt, oriented as illustrated in FIG. 11,using a laser and an optical lens, according to some embodiments.

FIG. 15 illustrates an intraocular shunt having one or more dissolvablesections, according to some embodiments.

FIGS. 16A-22 illustrate cross-sectional views of an intraocular shunthaving one or more dissolvable sections, according to some embodiments.

FIG. 23 illustrates placement of a drug-eluting intraocular shunt,according to some embodiments.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth to provide a full understanding of the subject technology. Itshould be understood that the subject technology may be practicedwithout some of these specific details. In other instances, well-knownstructures and techniques have not been shown in detail so as not toobscure the subject technology.

As noted above, glaucoma filtration surgery can often result in anundesirably low intraocular pressure in the anterior chamber of the eyeand can often lead to hypotony. The present disclosure provides variousembodiments of methods and devices that can enable a clinician togenerally prevent hypotony after a glaucoma filtration surgery whileenabling the clinician to ensure adequate pressure relief by adjustingthe flow through an intraocular shunt. As used herein, the term “shunt”includes hollow microfistula tubes similar to the type generallydescribed in U.S. Pat. No. 6,544,249 as well as other structures thatinclude one or more lumens or other flow paths therethrough.

An aspect of some embodiments is the realization that there are variousunpredictable factors related to the success of a surgical intervention.Fundamentally, a successful surgical intervention relieves intraocularpressure without causing hypotony. In order to be successful, the flowthrough a shunt and the resulting intraocular pressure in the anteriorchamber must account for various unpredictable biological factors, suchas aqueous production amount, viscosity of the aqueous humor, and otherbiological outflow restrictions.

The biological outflow restrictions associated with a shunt depend onthe overall outflow resistance or restrictions of the targeted spacewhere the shunt is placed. The biological outflow restrictions of thesubconjunctival space, for example, depend on: (1) the strength andamount and thickness of the tenon adhesions, if present (e.g., placed abinterno); (2) the thickness and consistency of conjunctiva, which canallow more or less fluid to diffuse into the subconjunctival vessels andinto the tear film; (3) existing fibrotic adhesions; (4) the presence oflymphatic outflow pathways (some pathways may already exist at the timeof shunt placement, but often the lymphatic pathways can be created andincrease days and weeks after the flow has started); (5) the amount ofdiffusion into episcleral vessels; (6) the amount of fibrosis build-upafter implant placement (which can be triggered by aqueous humor, startforming in the first one to four weeks after surgery, and can lead to asignificant or total outflow restriction). Most of these factors varygreatly patient by patient and are for the most part currentlyunpredictable. The potential fibrotic response is the biggest changingfactor in biological outflow resistance and can range from nosignificant outflow restriction over the first three months post-op to atotal flow blockage within one week after surgery.

These patient variations and their dynamic nature post-operatively makeit very difficult to maintain an optimal intraocular pressure with a“static” shunt placement. A “static” shunt placement can be referred toas a procedure or surgery in which a shunt is implanted and maintainedwithout any change to its own flow resistance parameters or shuntoutflow resistance, such as length, lumen diameter, or other featuresthat would affect the flow rate through the shunt. Thus, excludingbiological flow resistance changes in the target space, such as thosementioned immediately above, a “static” shunt or “static” shuntplacement will not result in variations to the flow parameters or shuntoutflow resistance of the shunt.

A static shunt usually provides substantial outflow in the early post-opphase (one day to two weeks) due to the absence of fibrotic tissue (orother biological outflow restrictions) early on. This can often lead toa less than desirable intraocular pressure in the anterior chamber forthis early phase, often hypotony, and an increased risk forcomplications associated with such low intraocular pressures. Then,after the initial phase (e.g., after a few days to a few weeks), somepatients experience a strong fibrotic response that can create highbiological outflow restrictions that can result in a higher than desiredintraocular pressure (e.g., above 20 mmHg).

Some embodiments disclosed herein provide a manner to overcome thesecomplications and uncertainties of traditional surgery. For example, aflow-tunable shunt can be provided that can be modified or self-adjustafter the surgery to maintain an optimal outflow resistance that cancompensate for an increase in biological outflow resistance. This canallow a clinician to monitor and maintain an optimal intraocularpressure throughout changing tissue stages (e.g., changes in thebiological outflow restriction of the targeted space, such as thosementioned above) that usually increase the biological outflow resistanceand lead to higher intraocular pressures.

Therefore, in some embodiments, shunt devices and methods of use canprovide: (1) substantial initial outflow resistance in order to avoidearly low post-op intraocular pressures and hypotony; and (2) subsequentlessening of outflow resistance to compensate for a rising biologicaloutflow resistance (e.g., fibrosis of the targeted space). The shunt canbe configured such that the flow resistance is manually or surgicallytuned by the clinician or specifically configured to self adjust (e.g.,through the use of dissolvable sections) over time.

Methods for Shunt Placement

Various structures and/or regions of the eye having lower pressure thathave been targeted for aqueous humor drainage include Schlemm's canal,the subconjunctival space, the episcleral vein, the suprachoroidalspace, the intra-tenon space, and the subarachnoid space. Shunts may beimplanted using an ab externo approach (e.g., entering through theconjunctiva and inwards through the sclera) or an ab interno approach(e.g., entering through the cornea, across the anterior chamber, throughthe trabecular meshwork and sclera). For example, ab interno approachesfor implanting an intraocular shunt in the subconjunctival space areshown for example in Yu et al. (U.S. Pat. No. 6,544,249 and U.S. PatentPublication No. 2008/0108933) and Prywes (U.S. Pat. No. 6,007,511), thecontents of each of which are incorporated by reference herein in itsentirety.

Some methods can involve inserting into the eye a hollow shaftconfigured to hold an intraocular shunt. In certain embodiments, thehollow shaft can be a component of a deployment device that may deploythe intraocular shunt. The hollow shaft can be coupled to a deploymentdevice or be part of the deployment device itself. Deployment devicesthat are suitable for deploying shunts according to the inventioninclude, but are not limited to the deployment devices described in U.S.Pat. Nos. 6,007,511, 6,544,249, and U.S. Publication No. US2008/0108933,the contents of each of which are incorporated herein by reference intheir entireties. The deployment devices can include devices such asthose as described in co-pending and co-owned U.S. patent applicationSer. No. 12/946,222, filed on Nov. 15, 2010, U.S. patent applicationSer. No. 12/946,645, filed on Nov. 15, 2010, and co-pending U.S.application Ser. No. 13/314,939, filed on Dec. 8, 2011, the contents ofeach of which are incorporated by reference herein in their entireties.

The shunt can be deployed from the shaft into the eye such that theshunt forms a passage from the anterior chamber into an area of lowerpressure, such as Schlemm's canal, the subconjunctival space, theepiscleral vein, the suprachoroidal space, the intra-tenon space, thesubarachnoid space, or other areas of the eye. The hollow shaft is thenwithdrawn from the eye. Methods for delivering and implantingbioabsorbable or permanent tubes or shunts, as well as implantationdevices for performing such methods, are generally disclosed inapplicant's co-pending applications, U.S. application Ser. No.13/314,939, filed on Dec. 8, 2011, and U.S. Application No.US2012/0197175, filed on Dec. 8, 2011, as well as in U.S. Pat. Nos.6,544,249 and 6,007,511, each of which are incorporated by reference intheir entireties. Embodiments of the shunts disclosed herein can beimplanted using such methods and others as discussed herein.

Some methods can be conducted by making an incision in the eye prior toinsertion of the deployment device. However, in some instances, themethod may be conducted without making an incision in the eye prior toinsertion of the deployment device. In certain embodiments, the shaftthat is connected to the deployment device has a sharpened point or tip.In certain embodiments, the hollow shaft is a needle. Exemplary needlesthat may be used are commercially available from Terumo Medical Corp.(Elkington, Md.). In some embodiments, the needle can have a hollowinterior and a beveled tip, and the intraocular shunt can be held withinthe hollow interior of the needle. In some embodiments, the needle canhave a hollow interior and a triple ground point or tip.

Some methods can be conducted without needing to remove an anatomicalportion or feature of the eye, including but not limited to thetrabecular meshwork, the iris, the cornea, or aqueous humor. Somemethods can be conducted without inducing substantial ocularinflammation, such as subconjunctival blebbing or endophthalmitis. Somemethods can be achieved using an ab interno approach by inserting thehollow shaft configured to hold the intraocular shunt through thecornea, across the anterior chamber, through the trabecular meshwork,and into the intra-scleral or intra-tenon space. However, some methodsmay be conducted using an ab externo approach.

In some methods conducted using an ab interno approach, the angle ofentry through the cornea can be altered to affect optimal placement ofthe shunt in the intra-tenon space. The hollow shaft can be insertedinto the eye at an angle above or below the corneal limbus, in contrastwith entering through the corneal limbus. For example, the hollow shaftcan be inserted from about 0.25 mm to about 3.0 mm above the corneallimbus. The shaft can be inserted from about 0.5 mm to about 2.5 mmabove the corneal limbus. The shaft can also be inserted from about 1.0mm to about 2.0 mm above the corneal limbus, or any specific valuewithin any of these ranges. For example, the hollow shaft can beinserted above the corneal limbus at distances of about: 1.0 mm, 1.1 mm,1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, or 2.0mm.

Further, in some embodiments, placement of the shunt farther from thelimbus at the exit site, as provided by an angle of entry above thelimbus, can provide access to more lymphatic channels for drainage ofaqueous humor, such as the episcleral lymphatic network, in addition tothe conjunctival lymphatic system. A higher angle of entry also resultsin flatter placement in the intra-tenon space so that there is lessbending of the shunt.

As discussed in Applicant's co-pending application, U.S. applicationSer. No. 13/314,939, filed on Dec. 8, 2011, the entirety of which isincorporated herein by reference, in certain embodiments, to ensureproper positioning and functioning of the intraocular shunt, the depthof penetration into the intra-tenon space may be important whenperforming some methods.

In some methods, the distal tip of the hollow shaft can pierce thesclera and intra-tenon space without coring, removing or causing majortissue distortion of the surrounding eye tissue. The shunt is thendeployed from the shaft. Preferably, a distal portion of the hollowshaft (as opposed to the distal tip) completely enters the intra-tenonspace before the shunt is deployed from the hollow shaft.

In accordance with some embodiments, the hollow shaft can comprise aflat bevel needle, such as a needle having a triple-ground point. Thetip bevel can first pierce through the sclera and into the intra-tenonspace by making a horizontal slit. In some methods, the needle can beadvanced even further such that the entire flat bevel penetrates intothe intra-tenon space, to spread and open the tissue to a full circulardiameter.

Further, in accordance with an aspect of some methods, the intra-tenonchannel can be urged open by the flat bevel portion of the needle sothat the material around the opening is sufficiently stretched and apinching of the shunt in that zone is avoided, thus preventing the shuntfrom failing due to the pinching or constriction. Full entry of the flatbevel into the intra-tenon space causes minor distortion and trauma tothe local area. However, this area ultimately surrounds and conforms tothe shunt once the shunt is deployed in the eye.

With reference to the figures, FIG. 1 is a schematic diagram thatillustrates a manner of accessing the eye and delivering an intraocularshunt for treatment of glaucoma. As noted, some methods disclosed hereinprovide for an ab interno approach. As also noted, the ab internoapproach may not be needed in order to perform the procedures or methodsdisclosed herein. For example, the shunt can be delivered using an abexterno approach, as discussed herein.

FIG. 1 illustrates the general anatomy of an eye 2. As illustrated, ananterior aspect of the anterior chamber 10 of the eye 2 is the cornea12, and a posterior aspect of the anterior chamber 10 of the eye 2 isthe iris 14. Beneath the iris 14 is the lens 16. The conjunctiva 18 is athin transparent tissue that covers an outer surface of the eye 2. Theanterior chamber 10 is filled with aqueous humor 20. The aqueous humor20 drains into a space(s) 22 below the conjunctiva 18 through thetrabecular meshwork (not shown in detail) of the sclera 24. The aqueoushumor 20 is drained from the space(s) 22 below the conjunctiva 18through a venous drainage system (not shown).

FIG. 1 illustrates a surgical intervention to implant an intraocularshunt into the eye using a delivery device 40 that holds the shunt, anddeploying the shunt within the eye 2. FIG. 1 illustrates an ab internoapproach in which the delivery device 40 has been inserted through thecornea 12 into the anterior chamber 10. As noted above, however, theimplant can also be placed using an ab externo approach, in which theconjunctiva or tenons can be dissected and pulled back, prior toplacement of a shunt.

Referring to FIG. 1, the delivery device 40 can be advanced across theanterior chamber 10 in what is referred to as a transpupil implantinsertion. The delivery device can be inserted through the anteriorangle and advanced through the sclera 24 until accessing a targetedspace, such as Schlemm's canal, the subconjunctival space, theepiscleral vein, an episcleral bleb, the suprachoroidal space, theintra-tenon space, the sub-tenon's space, the subarachnoid space, acreated intrascleral space, or other areas, as desired. The shunt isthen deployed from the deployment device, producing a conduit betweenthe anterior chamber and the targeted space to allow aqueous humor todrain through the traditional drainage channels of the eye, such as theintra-scleral vein, the collector channel, Schlemm's canal, thetrabecular outflow, the uveoscleral outflow to the ciliary muscle, theconjunctival lymphatic system, or others.

In some embodiments, the delivery device 40 can comprise a hollow shaft42 that is configured to hold an intraocular shunt. The shaft may holdthe shunt within the hollow interior of the shaft. Alternatively, thehollow shaft may hold the shunt on an outer surface of the shaft.

FIG. 2 provides a cross-sectional view of a portion of the eye 2, andprovides greater detail regarding certain anatomical structures of theeye and placement of an intraocular shunt 50. In particular, FIG. 2shows the shunt 50 implanted in the intra-tenon space between theconjunctiva 18 and the sclera 24. In some embodiments, intra-tenonplacement can be achieved by not dissecting the conjunctiva, bycontrolling the scleral exit location, and by pre-treatment of theintra-tenon space before or by tenon manipulation during the procedure.Placement of shunt 50 within the intra-tenon space allows aqueous humor20 to diffuse into the subconjunctival space. According to someembodiments, the outflow restrictions of the subconjunctival space candepend on the strength, amount, and thickness of the tenon adhesions (ifpresent, e.g., when placed ab interno), the thickness and consistency ofthe conjunctiva (which can allow more or less fluid to diffuse into thesubconjunctival vessels and tear space), and existing fibroticadhesions.

FIG. 2 illustrates one of a variety of potential placements of the shunt50 in the eye. As discussed herein, methods and devices provided hereincan be implemented wherein a shunt is placed in communication with otheranatomical features of the eye. Thus, some methods and devices disclosedherein can be implemented when a shunt forms a passage from the anteriorchamber into an area of lower pressure, such as Schlemm's canal, thesubconjunctival space, the episcleral vein, the suprachoroidal space,the intra-tenon space, the subarachnoid space, or other areas of theeye.

The methods of implantation may be fully automated, partially automated(and, thus, partially manual), or completely manual. For example, in afully automated procedure, a shunt may be delivered by roboticimplantation whereby a surgeon controls the advancement of the needle,plunger, optional guidewire and, as a result, shunt by remotelycontrolling a robot. In such fully automated, remotely controlledprocedures, the surgeon's hands typically do not contact implantationapparatus during the surgical procedure. Alternatively, shunt may bedelivered to the desired area of the eye with a “handheld” implantationapparatus. Handheld implantation devices, as well as details regardingsteps and procedures of implantation methods, are described inco-pending U.S. Application Publication Nos. 2012/0197175, filed on Dec.8, 2011 and Ser. No. 13/314,939, filed on Dec. 8, 2011, the entiretiesof each of which are incorporated herein by reference. Insertion of theneedle into the eye as well as certain repositioning or adjusting stepsmay be performed manually by the surgeon. In the case of fully manualdevices and methods, all of the positioning, repositioning, adjustingand implantation steps can be performed manually by the surgeon.

Intraocular Shunt Devices

Some embodiments disclosed herein comprise intraocular shunts that areconfigured to form a drainage pathway from the anterior chamber of theeye to a targeted space. In this manner, the shunt can allow aqueoushumor to drain from the anterior chamber and out through the traditionaldrainage channels of the eye, such as the intra-scleral vein, thecollector channel, Schlemm's canal, the trabecular outflow, theuveoscleral outflow to the ciliary muscle, the conjunctival lymphaticsystem, or others.

Some embodiments disclosed herein comprise a shunt that is generallycylindrically shaped with an outside cylindrical wall and, in someembodiments, a hollow interior that extends at least partially along thelength of the shunt. The shunt can have an inner wall defining a mainsection inner diameter, lumen dimension, diameter or a flow pathcross-sectional dimension or diameter of from about 10 μm to about 300μm. The shunt can have an inner wall defining a lumen dimension ordiameter of from about 50 μm to about 250 μm. Further, the shunt canhave an inner wall defining a lumen dimension or diameter of from about100 μm to about 200 μm. In some embodiments, the shunt can have an innerwall defining a lumen dimension or diameter of about 150 μm.

The inner diameter of the partially restrictive section can be fromabout 10 μm to about 70 μm. In some embodiments, the partiallyrestrictive section inner diameter can be from about 25 μm to about 55μm. In some embodiments, the partially restrictive section innerdiameter can be about 40 μm.

The outside dimension or diameter of the wall of some embodiments can befrom about 190 to about 300 μm. Further, the wall thickness of someembodiments can be from about 30 μm to about 70 μm.

In some embodiments, the intraocular shunt can have a length that issufficient to form a drainage pathway from the anterior chamber of theeye to the targeted space. The length of the shunt is important forachieving placement specifically in the targeted space. A shunt that istoo long will extend beyond the targeted space and may irritate the eye.For example, if the targeted space is the intra-scleral space, a shuntthat is too long can irritate the conjunctiva which can cause thefiltration procedure to fail. Further, in such embodiments, a shunt thatis too short will not provide sufficient access to drainage pathwayssuch as the episcleral lymphatic system or the conjunctival lymphaticsystem.

In some embodiments, the shunt may be any length that allows fordrainage of aqueous humor from an anterior chamber of an eye to thetargeted space. In some embodiments, the shunt can have a total lengthin the range of from about 1 mm to about 12 mm. The length can also bein the range of from about 2 mm to about 10 mm or from about 4 mm toabout 8 mm, or any specific value within said ranges. In someembodiments, the length of the shunt is from about 6 mm to about 8 mm,or any specific value within this range, for example, such as about: 6.0mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9mm, 7 mm, 7.1 mm, 7.2 mm, 7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8mm. 7.9 mm, or 8.0 mm.

Of the total shunt length, the length of the partially restrictivesection can be from about 0.2 mm to about 6 mm. In some embodiments, thepartially restrictive section length can be from about 1 mm to about 4mm. In some embodiments, the partially restrictive section length can beabout 2 mm.

Additionally, some embodiments of the shunt can have different shapesand different dimensions that may be accommodated by the eye. Inaccordance with embodiments disclosed herein, the intraocular shunt canbe formed having dimensions within the various ranges of dimensionsdisclosed for outer diameter (e.g., of the main section or partiallyrestrictive section), inner diameter (e.g., of the main section orpartially restrictive section), segment lengths (e.g., of the partiallyrestrictive section or main section), and total length.

For example, some embodiments can be configured such that the shunt hasa total length of about 6 mm, a main section inner diameter of about 150μm, and a partially restrictive section inner diameter of from about 40μm to about 63 μm.

Surgeon-Controlled Flow-Tunable Shunts

The figures illustrate embodiments of an intraocular implant or shuntthat can have a first flow that can be modified to a second flow bychanging the configuration of the implant.

Some implants can be configured to have a first flow that can be changedto a second flow by shortening the length of the implant. Some implantscan be configured to have a first flow that can be changed to a secondflow by removing a restrictive section thereof. In some embodiments, thefirst flow can be less than the second flow through the implant. Thus,modification, shortening, or removal of a section thereof can increasethe flow through the implant.

For example, the figures illustrate embodiments and configurations offlow-tunable implants or shunts having one or more partially obstructiveor flow-limiting restrictive sections and one or more unobstructive orunrestrictive main sections.

Embodiments of the shunts disclosed herein can provide a desired initialflow resistance or flow value that prevents excessive outflow from theanterior chamber of the eye, thus avoiding low intraocular pressures orhypotony. However, upon development of biological outflow resistance, aclinician can tune the flow resistance or flow value of the shunt toprevent high intraocular pressure. Accordingly, embodiments hereinenable a clinician to adjust or tune the flow rate of the shunt. Thegeometric configuration and dimensions of components of these shunts canbe manipulated as desired to provide a desired flow resistance.Accordingly, the embodiments illustrated and discussed do not limit thescope of the features or teachings herein.

In accordance with some embodiments, the shunt can be configured suchthat the clinician can adjust the flow resistance or flow value toprovide a flow rate of from about 1 μL per minute to about 3 μL perminute. Further, the shunt can be configured such that the clinician canadjust the flow resistance or flow value to provide a flow rate of about2 μL per minute.

FIG. 3 illustrates a shunt 100 having an elongate body having an innerwall 102 that defines a shunt lumen 104 extending therethrough. Theshunt 100 can comprise opposing ends 106, 108 (inlet/outlet). The end106 can be a restrictive end, and the end 108 can be a clear end. Theshunt 100 can comprise a partially obstructive or flow-limitingrestrictive section 110 and a unobstructive or unrestrictive mainsection 112. Flow can be provided through the partially restrictivesection 110, but with greater resistance than through the main section112. The shunt lumen 104 can extend through the main section 112. Thepartially restrictive section 110 can comprise a gelatin tube. Thegelatin tube can be inserted into the shunt lumen 104. The a partiallyrestrictive section 110 or gelatin tube can comprise a wall 118 thatdefines a secondary lumen 120. The wall 118 can define a different innerdimension than the wall 102. For example, the wall 118 can define across-section or profile that is smaller than the cross-section orprofile of the wall 102, thus rendering the lumen 104 larger than thelumen 120. In some embodiments, the secondary lumen 120 can extendgenerally coaxially with the shunt lumen 104; however, the secondarylumen 120 can be configured to be spaced apart from a central axis ofthe shunt lumen 104.

For example, the secondary lumen 120 can also extend longitudinallyalong the partially restrictive section 110 while traversing and/orbeing spaced apart from the central axis of the partially restrictivesection 110. Thus, the wall 118 can define a variable thickness.Further, the secondary lumen 120 can be encircled by the wall 118forming the partially restrictive section 110. However, the wall 118 canbe discontinuous, and the secondary lumen 120 can be boundedintermediate the wall 118 of the partially restrictive section 110 andthe wall 102. Thus, the lumen 104 and the lumen 120 can have a boundarysurface in common, in some embodiments.

Further, the partially restrictive section 110 can be attached to theshunt 100 either permanently or removably. For example, the partiallyrestrictive section 110 can be a separate piece that is permanentlyattached to the shunt 100 or formed with the shunt 100 as a singlepiece. However, the partially restrictive section 110 can also beremovably attached to the shunt 100, thereby allowing the partiallyrestrictive section 110 to be completely or at least partially removedfrom the shunt 100. For example, the partially restrictive section 110can be a metal stylus or structure that is inserted into the shunt lumen104, which can later be removed.

The shunt 100 can be configured such that two or more sections thereofcomprise different flow restrictions or flow values. Thus, in someinstances, a clinician can manually manipulate or adjust the overallflow restriction or flow value of the shunt 100 by manipulating one ormore sections of the shunt 100. Further, in some instances, a cliniciancan utilize a shunt or shunt system that self-adjusts or passivelyadjusts to change the overall flow restriction or flow value of theshunt over time.

The flow resistance or flow value of a given section of the shunt canrelate to the geometric constraints or properties of the given section.The geometric constraints or properties can be one or more of thediameter or radius, the length of the given section, a cross-sectionalarea of the flow passage, surface roughness, or other such geometricscharacteristics. In some embodiments, for purposes of this disclosure,the flow resistance or flow value can be a numeric representation,coefficient, or formula upon which the mathematical calculation for afluid flow rate through the given section for a given fluid ispredicated. For example, the flow value can represent a ratio of aninner diameter or radius and an axial length of the given section. Ahigher flow value could result in a higher flow rate. Further, in someembodiments, the flow resistance can be the inverse of the flow value,e.g., a ratio of an axial length and an inner diameter or radius of thegiven section. Generally, a higher flow resistance would result in alower flow rate. Further, the flow resistance can depend mainly on theshunt length, inner diameter and viscosity of the liquid (AqueousHumor).

The flow through the shunt, and thus the pressure exerted by the fluidon the shunt, is calculated by the Hagen-Poiseuille equation:

$\Phi = {\frac{\mathbb{d}V}{\mathbb{d}t} = {{v\;\pi\; R^{2}} = {{\frac{\pi\; R^{4}}{8\eta}\left( \frac{{- \Delta}\; P}{\Delta\; x} \right)} = {\frac{\pi\; R^{4}}{8\eta}\frac{{\Delta\; P}}{L}}}}}$where Φ is the volumetric flow rate; V is a volume of the liquid poured(cubic meters); t is the time (seconds); v is mean fluid velocity alongthe length of the tube (meters/second); Δx is a distance in direction offlow (meters); R is the internal radius of the tube (meters); ΔP is thepressure difference between the two ends (pascals); η is the dynamicfluid viscosity (pascalsecond (Pa·s)); and L is the total length of thetube in the x direction (meters).

For example, the shunt 100 can be configured such that the flow throughthe partially restrictive section 110 defines a first flow resistance orflow value. The main section 112 can define a first flow cross-sectionalarea, and the partially restrictive section 110 can define a second flowcross-sectional area that is less than the first flow cross-sectionalarea. The first flow resistance or flow value can be determined bygeometric constraints or properties of the partially restrictive section110. Such constraints can include the length of the partiallyrestrictive section 110, the inner diameter or radius of the wall 118,and other features, such as an inner surface roughness of the wall 118.

Further, the second flow cross-sectional area or profile of thepartially restrictive section 110 can be any of a variety of geometricprofiles. For example, the second flow cross-sectional area or profilecan be circular, rectangular, square, polygonal, or otherwise shaped.The second flow cross-sectional area or profile can be configured toprovide less cross-sectional area than the main section 112. The secondflow cross-sectional area or profile can be constant or variable alongthe longitudinal extent of the partially restrictive section 110.

Similarly, the main section 112 can define a flow resistance or flowvalue that is different than the first flow resistance or flow value ofthe partially restrictive section 110. As with the first flow resistanceor flow value, the flow resistance or flow value of the main section 112can be determined by geometric constraints or properties of the mainsection 112, as discussed above. Accordingly, the geometric constraintsof the main section 112 can differ from the geometric constraints of thepartially restrictive section 110, resulting in different flowresistances or flow values.

The total pressure drop across the shunt ΔP_(total) consisting of a mainsection and a partially constrained section can be calculated for eachsection separately as ΔP_(main) and ΔP_(partially constrained),according to the formula above:

${\Delta\; P} = \frac{8{\Phi\eta}\; L}{\pi\; R^{4}}$and then by adding the two numbers together:ΔP_(total)=ΔP_(main)+ΔP_(partially constrained). If there are more than2 sections, then they are added together accordingly.

ΔP_(total) for any given shunt represents the minimum IOP in the eye forany given flow rate Φ. The flow rate Φ through the shunt is depending onthe shunt location and amount of surrounding tissue resistance normallyfrom about 10% to about 90% of the amount of aqueous production in theeye which is typically from about 1 to about 3 μl/min.

As illustrated in FIGS. 3-4, the shunt wall 102 can be configured suchthat the lumen 104 is large for most of the shunt length, which wouldprovide very little flow resistance. However, the inner dimension of thewall 118 of the partially restrictive section 110 can be much smallerthan the inner dimension of the wall 102, which can constrain flowthrough the shunt 100 to the first flow resistance or flow value.

As illustrated in FIGS. 3-4, the shunt 100 can comprise a singlepartially restrictive section 110 and a single main section 112.However, the shunt 100 can comprise multiple partially restrictivesections and multiple main sections (see related embodiments shown inFIGS. 18-19).

A given partially restrictive section can also define a plurality ofcross-sectional flow areas or inner diameters. For example, asillustrated in FIG. 5, the partially restrictive section can havedistinct steps or subsections that have distinct cross-sectional flowareas or inner diameters.

FIG. 5 illustrates an embodiment of a shunt 140 in which a partiallyobstructive or flow-limiting restrictive section 142 comprises first andsecond occluding components 150, 152. The first occluding component 150and the second occluding component 152 can be inserted into a lumen 144,formed by a shunt wall 146 of the shunt 140. The first and secondoccluding component 150, 152 can also be pre-assembled prior toinsertion into the shunt lumen 144. The first and second occludingcomponents 150, 152 can define different inner cross-sectionaldimensions (e.g., diameters) that provide distinct flow resistances orflow values. Accordingly, in some embodiments, a clinician can adjust orconfigure more than two flow resistances or flow values to manipulatethe overall flow resistance or flow value of the shunt.

In some embodiments, the partially restrictive section can be formedusing a material or component that is formed separately from therestrictive end and later joined thereto.

For example, similar to the embodiment illustrated in FIG. 5, thepartially restrictive section can be formed using a tube configured tofit within the shunt lumen. Further, the partially restrictive sectioncan be formed using a component, coating, or other material that islayered along the inner surface of the shunt wall. The component,coating, or other material can extend at least partially about thecircumference of the inner surface of the shunt wall. In someembodiments, the component, coating, or other material can extend fullyabout the circumference, and in some embodiments, the component,coating, or other material can extend longitudinally along the innersurface of the shunt wall. In any configuration, the overallcross-sectional flow area of the partially restrictive section can beless than the overall cross-sectional flow area of the main section.

In some embodiments, a partially restrictive section can be formed byvarying a dimension of the shunt along that partially restrictivesection. Thus, the partially restrictive section can be formedintegrally or of a single, continuous piece of material with the shunt.

For example, as illustrated in FIG. 6, another embodiment of a shunt 180is illustrated in which a partially obstructive or flow-limitingrestrictive section 182 is formed integrally or as a single, continuouspiece with a main section 184 of the shunt 180. In these embodiments, alumen 186 defined by a wall 188 of the shunt 180 tapers towards arestrictive end 190 thereof as the thickness of the wall 188 increases.The tapering can be linear or nonlinear. In either configuration, thetapering of the shunt lumen 186 will tend to create a change in the flowresistance or flow value between the main section 184 and the partiallyrestrictive section 182. Additionally, the tapering can be stepwise, assimilarly shown in the embodiment of FIG. 5.

FIG. 7 illustrates yet another embodiment of a shunt 200 having aplurality of partially obstructive or flow-limiting restrictive sections202, 204 and a plurality of main sections 206, 208. The partiallyrestrictive sections 202, 204 can comprise identical or different flowresistances or flow values. As illustrated, the partially restrictivesection 202 can define a slightly longer axial length than the partiallyrestrictive section 204. Accordingly, the flow resistance for thepartially restrictive section 202 can be greater than the flowresistance for the partially restrictive section 204. In someembodiments, the inner diameter or radius of the partially restrictivesections 202, 204 can also vary. Further, the main section 206 can bedisposed between the partially restrictive sections 202, 204.

As with any of the geometric parameters of embodiments taught ordisclosed herein, the distance between the partially obstructive orflow-limiting restrictive sections 202, 204 can be varied in order toachieve a desired overall flow resistance or flow value for the shunt.

Methods for Adjusting Shunt Flow Resistance

Using a flow-tunable shunt disclosed and taught herein, a clinician canmodify the flow resistance or flow value of one or more portions of theshunt to adjust the overall flow resistance or flow value of the shunt.This allows the clinician to ensure that the shunt maintains an optimaloverall flow resistance in response to any increase in biologicaloutflow resistance. Thus, during postoperative visits, the clinician canmonitor any changes in the tissue surrounding the shunt or the drainagechannels, measure and track the intraocular pressure, and whennecessary, adjust or modify the flow resistance or flow value in orderto maintain an optimal intraocular pressure.

As noted above, after a shunt is placed in the eye has healed, thesurrounding tissue can create biological outflow resistance, such asfibrosis, which can limit or reduce the flow through the shunt. Thetissue reaction that changes the overall outflow resistance of the shunttypically stabilizes after about 1-10 weeks after the surgery.

A clinician can conduct a post-operative checkup to modify the shunt ina subsequent procedure after a threshold period of time has passed. Thisperiod of time can be from about eight weeks to about three months.Often, ten weeks can be a sufficient amount of time in order to achievestabilization and healing. If appropriate, the modification of the shuntcan be performed as a matter of course.

As part of the post-operative checkup, the clinician can verify whetherthe intraocular pressure is at a desired level. Generally, normalintraocular pressure is from about 10 mmHg and about 20 mmHg. Should theintraocular pressure be at an undesirable level (e.g., greater than 20mmHg), the clinician can modify the shunt accordingly.

The clinician can modify the shunt to reduce the flow resistance or flowvalue of the shunt. For example, the clinician can cut the shunt, and insome cases, remove a portion thereof from the eye. The cutting of theshunt can increase the flow through the shunt, thereby relieving andreducing the intraocular pressure.

Accordingly, in some embodiments, methods and devices are provided bywhich a shunt can provide: (1) substantial initial outflow resistance inorder to avoid early low post-op intraocular pressures and hypotony, and(2) the ability to subsequent reduce outflow resistance to compensatefor a rising biological outflow resistance (e.g., fibrosis of thetargeted space).

Mechanical Modification of the Shunt

In order to change the flow resistance or flow value of the shunt, someembodiments of the shunt can be configured such that the clinician cansplice, cut, puncture, or otherwise remove one or more aspects,fragments, or sections or all of the partially obstructive orflow-limiting restrictive section (s) of the shunt. In some instances,the clinician can cut off a portion of the restrictive end of the shuntand thereby open up the flow for an optimal long-term intraocularpressure performance.

In some methods, the shunt can be positioned such that a restrictive endis disposed in the anterior chamber of the eye. Further, in somemethods, the shunt can be positioned such that a restrictive end isdisposed in the targeted space or a location of lower pressure.Furthermore, in some embodiments, the shunt can be configured andpositioned such that one or more partially obstructive or flow-limitingrestrictive sections or ends are situated in the anterior chamber andthe targeted space.

For example, FIG. 8 illustrates a shunt 300 that is implanted into aneye 302. The shunt 300 can comprise a restrictive end 304 and a clearend 306. The restrictive end 304 can be positioned in the anteriorchamber 310 of the eye 302. Further, the clear end 306 can be placed ina subconjunctival space 320 of the eye 302. Thus, the shunt 300 can beoperative to provide pressure relief of the fluid in the anteriorchamber 310 to a location of lower pressure, the subconjunctival space320 of the eye 302. As noted above, while the restrictive end 304 cantend to ensure that the condition of low intraocular pressure isavoided, such as hypotony, over time, certain biological outflowrestrictions can be formed, which can reduce the overall outflow or flowrate of the shunt 300. Accordingly, a clinician can modify the shunt 300in order to change the flow resistance or flow value of the shunt 300 tocompensate for later-developing biological outflow restrictions.

FIG. 9-11 illustrate different aspects of embodiments in which the shuntcan be mechanically modified. For example, FIG. 9 illustrates anembodiment of a method for mechanically modifying the shunt 300 in orderto adjust the flow resistance or flow value of the shunt 300. Asillustrated, a mechanical cutting device 340 can be moved into theanterior chamber 310 of the eye 302. The cutting device 340 can compriseone or more sharpened portions configured to engage or cut the shunt300. For example, the cutting device 340 can comprise a needle having asharpened end, scissors, or other micro devices suitable for use in theeye 302.

Once the cutting device 340 is moved into the anterior chamber 310, aportion 342 of the restrictive end 304 can be removed from the shunt300. The portion 342 can be all or part of a partially obstructive orflow-limiting restrictive section 352 of the shunt 300. As illustrated,in some embodiments, the portion 342 can be an entirety of the partiallyrestrictive section 352 of the shunt 300, which can be removed from theshunt 300 by cutting the shunt 300 at a location distal to the partiallyrestrictive section 352 of the restrictive end 304. Thereafter, inembodiments in which the shunt 300 comprises only a single partiallyrestrictive section, such as partially restrictive section 352, theremainder of the shunt 300 will be the main portion, which can havegenerally a constant cross-sectional area and/or profile. As such, byremoving the portion 342, the flow resistance of the shunt 300 willdecrease. Further, the flow value of the shunt 300 will increase.

Some embodiments of the method can be implemented such that only aportion of the partially restrictive section 352 is removed from theshunt 300. For example, the cutting device 340 can cut the shunt 300such that half of the partially restrictive section 352 remainsinterconnected with the shunt 300. As such, although the flow resistanceof the shunt 300 will decrease, the flow resistance will be higher thanit otherwise would be if the entire partially restrictive section 352were removed. Various implementations of methods can be performed suchthat more or less of a partially restrictive section(s) are removedduring a modification procedure. Accordingly, a clinician canselectively tune the flow resistance or flow value of the shunt based onspecific parameters or properties of the surrounding tissue and theshunt.

In accordance with some embodiments, the shunt can also be positionedsuch that the restrictive end thereof is positioned in the targetedspace or location of lower pressure, such as in the subconjunctivalspace of the eye. For example, FIG. 10 illustrates a shunt 380 having apartially obstructive or flow-limiting restrictive section 382 in arestrictive end 384 thereof that is positioned in the subconjunctivalspace 320. In such implementations, the partially restrictive section382 or restrictive end 384 of the shunt 380 can be manipulated to adjustthe flow resistance or flow value of the shunt 380.

Similar to the embodiment discussed above in FIG. 9, a cutting devicecan be inserted into the subconjunctival space 320 in order to modifythe restrictive end 384.

For example, the cutting device can be a needle that cuts at least aportion or shunt fragment 390 of the restrictive end 384 from the shunt380. The cutting of the restrictive end 384 in the subconjunctival space320 can be achieved through a needle manipulation of the shunt 380. Thiscan be performed similar to a needling procedure, in which a 27GA or30GA needle is entered under the conjunctiva within a few millimetersfrom the restrictive end 384. The tip of the needle can then becarefully advanced toward the restrictive end 384. Subsequently, througha cutting motion, the tip of the needle can then cut a shunt fragment390 of the restrictive end 384 in order to adjust the flow resistance orflow value of the shunt 380. This needle procedure can also be performedat the slit lamp under topical numbing only. In some embodiments, suchas that illustrated in FIG. 10, the entire partially restrictive section382 can be severed from the shunt 300.

Referring now to FIG. 11, after the shunt 380 has been modified by thecutting device, the displaced or severed shunt fragment 390 of the shunt380 can be removed from or repositioned within the subconjunctival space320 in a position adjacent to a modified end 392 of the shunt 382. Forexample, the modified end 392 of the shunt 382 can be spaced apart fromthe shunt fragment 390 such that a small space or is present between themodified end 392 and the shunt fragment 390. In this manner, outflowthrough the modified end 392 can generally remain clear. In particular,the shunt fragment 390 can act as a spacer that will tend to preventblockage and preserve outflow through the modified end 392. This can beparticularly true for a shunt material that remains very quiet in theeye, such as a gelatin material. In some embodiments, the shunt fragment390 can be spaced apart from the modified end 392 by from about 0.2 mmto about 2 mm. Further, the shunt fragment 390 can be spaced apart fromthe modified end 392 by from about 0.5 mm to about 1 mm.

Laser Modification of the Shunt

Some embodiments of the shunts and methods disclosed herein can beprovided such that the shunt can be modified using a laser procedure.FIGS. 12-14 illustrate aspects of methods in which a shunt is modifiedusing a laser.

For example, FIG. 12 illustrates a method for modifying a shunt 400implanted in an eye 402. While FIG. 12 illustrates that the shunt 400can comprise a restrictive end 404 placed in an anterior chamber 406 ofthe eye 402, other implementations of methods can be provided in which arestrictive end is located in a targeted space or a location of lowerpressure. For example, FIGS. 13-14 illustrate a method for modifying ashunt 410 in an eye 412, wherein the shunt 410 includes a restrictiveend 414 disposed in a targeted space, shown as a subconjunctival space416 and an opposing end that extends into an anterior chamber 418 of theeye 412.

Similar to the embodiments discussed above with respect FIGS. 9-11, thelaser procedures for modifying the shunts 400, 410 can allow a clinicianto at least partially cut and/or separate a shunt fragment from thepartially obstructive or flow-limiting restrictive section of the shunt.The shunt fragment that is at least partially cut and/or separated fromthe shunt can be removed from the eye or left in place, as similarlydiscussed above (the details of which can also be implemented in laserembodiments). For example, in FIG. 12, a shunt fragment 408 that isseparated from the restrictive end 404 of the shunt 400 can be extractedfrom the anterior chamber 406.

However, in FIGS. 13-14, a shunt fragment 420 that is separated from theshunt 410 can either be removed from the subconjunctival space 416 orpositioned within the subconjunctival space 416 to act as a spacer, asdiscussed above with regard to FIG. 11. As similarly discussed abovewith respect to FIG. 11, after the shunt 410 has been modified by thelaser, the displaced or separated shunt fragment 418 of the shunt 410can be removed from or repositioned within the subconjunctival space 416in a position adjacent to a modified end 422 of the shunt 410.

For example, the shunt fragment 418 can be spaced apart from themodified end 422 of the shunt 410 such that a small space or gap ispresent between the modified end 422 and the shunt fragment 418. In thismanner, outflow through the modified end 422 can generally remain openand less restricted. The shunt fragment 418 can act as a spacer thatwill tend to prevent blockage, local fibrosis buildup and preserveoutflow through the modified end 422. In some embodiments, the shunt canadvantageously be fabricated from a material that remains very quiet inthe eye, such as a gelatin material. The shunt fragment 418 can bespaced apart from the modified end 422 by from about 0.2 mm to about 2mm. In some embodiments, the shunt fragment 418 can be spaced apart fromthe modified end 422 by from about 0.5 mm to about 1 mm.

In accordance with some methods, the laser procedure can be performedusing one or more lasers to modify the configuration of the shunt. Forexample, the laser can comprise a surgical or treatment beam and anaiming beam. The modification or laser cutting can be achieved by usinga single higher power laser or by crossing two or more lower powerlasers. In some instances, the laser procedure can be implemented usingtwo aiming beams that target a given location and then using one or moretreatment beams to modify the shunt.

In some methods, the treatment beam(s) can be a photodisruptive YAGlaser. The treatment beam(s) and the aiming beam(s) can also be used ina slit lamp configuration. For example, the laser implant cuttingprocedure can be performed by aligning a pair of aiming beams and thenpulsing one or more YAG lasers in a slit lamp configuration to targetand cut or modify the restrictive end of a shunt.

The treatment beam(s) can be pulsed at a wavelength of 532 nm, 635 nm,808 nm, 940 nm, 1053 nm, 1064 nm, 1120 nm, 1320 nm, 1440 nm, and/or 1540nm. In some embodiments, the wavelength can be 1064 nm.

The treatment beam(s) can be pulsed laser beam with a pulse duration of1 ns to 1 ms, a pulse repetition rate from single shot to 100 Hz and apulse energy from 0.2 mJ to 10 mJ. The pulse energy can be from about 2mJ to about 6 mJ.

In some embodiments the pulse duration can be 3 ns and the pulse energycan be 3 mJ.

The laser focusing angle is from about 10 degrees to about 30 degrees.The focusing angle can be from about 14 degrees to about 20 degrees.Further, in some embodiments, the focusing angle can be about 16degrees.

The treatment beam(s) can have a beam waist diameter or “spot size” offrom about 1 μm to about 20 μm. The spot size can be from about 6 μm toabout 15 μm. In some embodiments, the spot size can be about 8 μm.

According to some methods, two intersecting aiming beams (illustrated inFIGS. 12-14 as 426) can be overlapped at a target location. For example,in FIG. 12, the aiming beams 426 can be overlapped or crossed such thatan overlap point or target location 432 of the beams lies on or targetsa top surface 434 of the shunt 400 or conjunctival tissue above theshunt 400. In FIGS. 13 and 14, the aiming beams 426 can be overlapped orcrossed at an overlap point or target location 438, which can be alongthe top surface 434 of the shunt 410. However, in various methods, theoverlap points 432, 438 can be moved to another location as desired,such as along a bottom surface 442 of the shunt 410. When the aimingbeams 426 are properly aligned, one or more additional lasers can beused to modify the shunt.

Further, while the overlap point or target location of the aiming beams426 can be at a first location, the treatment beam(s) can be focused toa different point or second location. For example, the focus of thetreatment beam(s) can be adjusted to be deeper past the overlap point ortarget location, to extend further to the tissue. The focus of thetreatment beam(s) can be offset by a depth offset 440 (shown forexample, in FIG. 13). The depth offset 440 can be a distance beyond theoverlap point or target location where the laser beam is focused. Whilein some embodiments the depth offset 440 can be a depth as generallymeasured from the top or uppermost surface or edge of the shunt (whenthe overlap point or target location is at the top surface of theshunt), the depth offset 440 can also be generally measured from thebottom surface of the shunt (when the overlap point or target locationis at the bottom surface of the shunt). The depth offset 440 can be fromabout 50 μm to about 400 μm. In some embodiments, the depth offset canbe spaced at about 250 μm from the aiming beam intersection point.

According to some embodiments, the alignment of the treatment and aimingbeam(s), as well as the firing of the treatment beam(s) is done with amanual slit lamp actuator and fire bottom. Such embodiments can providesufficient precision to effectively implement the procedure.

With a proper alignment, the shunt 400, 410 can be modified (e.g., cutor broken) with a single shot at around 3 mJ pulse energy. According tosome embodiments, a reliable/typical cutting can be achieved with 3-5pulses placed in the same focal area with only minimal adjustments inbetween.

For example, as shown in FIG. 13, the aiming beams 426 can overlap atpoint 438 generally along the top surface 434 of a 300 μm diametergelatin shunt 410. The aiming beams 430 can be focused at a depth offsetof about 250 μm, which will focus the beams deeper toward the bottomsurface 442 of the shunt 410. In such embodiments, the intersectingaiming beams 430 will tend to be focused on the bottom surface 442 ofthe shunt 410, which will generally cause cracking and cutting of theshunt 410 from the bottom up. In this manner, any potential tissuedamage of the conjunctiva above the shunt 410 (e.g., conjunctivalperforations) can be avoided.

Additionally, in accordance with some methods, a lens 470 can be used toimprove accuracy of the targeting. By improving the accuracy, aclinician can avoid hitting a blood vessel with a laser pulse and thevisual obstruction that would result therefrom. Further, the use of alens 470 can also help create a better optical beam entrance interfaceinto the eye 412. In some methods, the lens 470 can be a small flat orplano-convex glass piece.

The lens 470 can be placed adjacent to the eye 412 near the location ofthe restrictive end 414 of the shunt 410. When placed adjacent to theeye 412, a convex side of the lens 470 can face down towards theconjunctiva/shunt. In some methods, the lens 470 can be pushed onto thearea over the implant during the laser cutting. Thereafter, thetreatment and aiming beam(s) can be utilized according to animplementation disclosed are taught herein.

Modification Through Dissolution

Additional methods and devices can also be provided in which aflow-tunable shunt provides early hypotony protection and a later,gradual lessening of the flow restriction without any post-op surgicalintervention (such as the cutting above). In some embodiments, whetherused independently of or in conjunction with other aspects ofembodiments disclosed herein, the shunt can also comprise anunobstructive or unrestrictive main section and a partially obstructive,restrictive, or flow-limiting dissolvable plug or section. The mainsection and/or the restrictive section can also be detachable orseparable from the shunt, as discussed in embodiments above.

The shunt can be configured such that flow can move more easily throughthe main section than through the partially restricted section. The mainsection can comprise a wall that defines a first flow cross-sectionalarea. The partially restrictive dissolvable section can comprise a wallthat defines an aperture, lumen, or channel through which fluid canpass, but with greater resistance than through the main section. Thus,in some embodiments, the presence of a dissolvable section can slow, butnot entirely restrict flow through the shunt. Instead, a dissolvablesection can be located so as to restrict flow at early stages after thesurgical procedure, but to dissolve over time, thereby increasing flowthrough the dissolvable section and hence, through the shunt.

In some embodiments, the shunt can comprise one or more partiallyrestrictive dissolvable sections. For example, the shunt can comprise apartially restrictive dissolvable section at a single end thereof. Theshunt can comprise two or more partially restrictive dissolvablesections, spaced close together or spaced apart from each other atopposing ends of the shunt. In some methods, a partially restrictivedissolvable section can be placed either in the anterior chamber or inan area of lower pressure, such as the subconjunctival space. An aspectof some embodiments is the realization that there may be an advantage toplacing a dissolvable section in the anterior chamber (compared withhaving the dissolvable section only in the subconjunctival space) due tothe possibility that particulate or debris could float into the shuntlumen and block flow through a dissolvable section in thesubconjunctival space.

Further, the partially restrictive section(s) can comprise a wall thatdefines an aperture, lumen, or channel. As noted similarly with regardto other embodiments above, the wall of the partially restrictivesection(s) can define a second flow cross-sectional area. The secondflow cross-sectional area can be less than the first flowcross-sectional area of the main section. In some embodiments, thewall(s) can define aperture(s), lumen(s), or channel(s) that aregenerally tubular. Further, the aperture(s), lumen(s), or channel(s) canbe square, polygonal, triangular, or other varieties of random shapes.The wall(s) can be configured such that the aperture(s), lumen(s), orchannel(s) can extend along a central axis of the partially restrictivesection(s). However, the aperture(s), lumen(s), or channel(s) can alsoextend longitudinally along the partially restrictive section whiletraversing and/or spaced apart from the central axis of the partiallyrestrictive section. Further, the aperture(s), lumen(s), or channel(s)can be encircled by the material forming the partially restrictivesection. However, the aperture(s), lumen(s), or channel(s) can also beformed intermediate the wall of the partially restrictive section andthe wall of the main section.

Additionally, the material forming the partially restrictive dissolvablesection(s) of the shunt can be configured to dissolve according to adesired dissolution rate, dissolution order, and/or dissolution pattern.A partially restrictive dissolvable section can comprise more than onetype of material. The material(s) can be layered axially,circumferentially offset, or otherwise positioned to provide adifferential or staged dissolution order or pattern. The material(s) canhave variable or different dissolution rates.

Referring to FIGS. 15-22, various embodiments of shunts having apartially restrictive section. FIG. 15 illustrates a shunt 500 having afirst end 502. The first end 502 comprises a partially restrictivesection 504. The partially restrictive section 504 can comprise amaterial that is loaded into a lumen 506, formed by a wall 508 of theshunt 500 or coated onto the shunt wall 508. For example, in someembodiments, the material of the partially restrictive section 504 canbe formed by dipping the shunt 500, coating the shunt 500, laminatingthe shunt 500, layering the shunt 500 over the partially restrictivesection 504, pushing a plug or tube of material into the shunt 500, orotherwise loading material onto the wall 508 or into the lumen 506.

FIGS. 16A-B illustrate the first end 504 at different stages ofdissolution. FIG. 16A illustrates an embodiment of the partiallyrestrictive section 504 prior to implantation and dissolution. Asillustrated generally, the partially restrictive section 504 comprisesan aperture or channel 510 for allowing at least some fluid flowtherethrough. Accordingly, for a short period after being installed, theshunt 500 will provide minimal flow therethrough, thus tending to avoidhypotony.

However, as shown in FIG. 16B, the partially restrictive section 504 candissolve over time such that the aperture or channel 510 will increasein size, thus permitting greater flow therethrough. In some embodiments,as the section 504 dissolves, the aperture or channel 510 will tend toapproximate or become generally the same dimension as the shunt wall508. Such dissolution can tend to increase flow in order to compensatefor later increased biological outflow restrictions.

The embodiments shown in FIGS. 17-19 illustrate shunts having more thanone partially restrictive section. These shunts can be configured tovary the number of partially restrictive sections, the length(s) of thepartially restrictive section(s), the inner diameter or size of theapertures or channels of the partially restrictive section(s), thematerial used for each partially restrictive section, spacing relativeto each other and the shunt, etc.

For example, FIG. 17 illustrates a shunt 550 having a pair of partiallyrestrictive sections 552 and 554 positioned at a first end 556 of theshunt 550. The sections 552, 554 are positioned contiguously without aspaced therebetween. FIG. 18 illustrates another shunt 570 havingpartially restrictive sections 572, 574, 576 positioned adjacent to eachother at a first end 578 of the shunt 570. While the sections 572, 574are positioned contiguously, the section 576 is spaced apart from theother sections 572, 574. FIG. 19 illustrates yet another shunt 590having first and second ends 592, 594. Each end 592, 594 comprises apartially restrictive section 596, 598.

FIGS. 20-22 also illustrate possible aspects of some embodiments. Forexample, FIG. 20 illustrates a shunt 610 having a partially restrictivesection 612. The partially restrictive section 612 can comprise axiallynested layers 614, 616. FIG. 21 illustrates a shunt 630 having apartially restrictive section 632. The partially restrictive section 632can have a variable diameter aperture or channel 634. Further, whilesome illustrated embodiments show that a partially restrictive sectioncan extend only to the end of the shunt or only within the shunt lumen,FIG. 22 illustrates a shunt 650 having a partially restrictive section652 that extends axially beyond an end 654 of the shunt 650. Theembodiments of FIG. 22 can be formed by dipping the shunt end 654 into adesired material, for example. As such, various embodiments can compriseany of a variety of geometries.

Shunt Materials

All or only a portion of a shunt may be dissolvable. For example, thedissolvable section can comprise a dissolvable biocompatible material.The material can be configured to dissolve over a set or desired periodof time, from days to months, based on how long hypotony protection isdesired.

In some embodiments, the material selected for the shunt can be agelatin or other similar material. In some embodiments, the gelatin usedfor making the shunt can be a gelatin Type B from bovine skin. Apreferred gelatin is PB Leiner gelatin from bovine skin, Type B, 225Bloom, USP. Another material that may be used in the making of theshunts is a gelatin Type A from porcine skin, also available from SigmaChemical. Such gelatin is available is available from Sigma ChemicalCompany of St. Louis, Mo. under Code G-9382. Still other suitablegelatins include bovine bone gelatin, porcine bone gelatin andhuman-derived gelatins. In addition to gelatins, microfistula shunt maybe made of hydroxypropyl methylcellulose (HPMC), collagen, polylacticacid, polyglycolic acid, hyaluronic acid and glycosaminoglycans.

The shunt material can be cross-linked. For example, when a gelatin isused, cross-linking can increase the inter- and intramolecular bindingof the gelatin substrate. Any means for cross-linking the gelatin may beused. In some embodiments, the formed gelatin shunts can be treated witha solution of a cross-linking agent such as, but not limited to,glutaraldehyde. Other suitable compounds for cross-linking include1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC). Cross-linking byradiation, such as gamma or electron beam (e-beam) may be alternativelyemployed.

The dissolvable section can comprise a material that is identical,similar, or different from the material of the shunt. In someembodiments, the dissolvable section material can be made out of agelatin, which can be similar to a gelatin used to make the shunt, withthe gelatins differing in the amount of crosslinking each has undergone.

In some embodiments, the shunt can be cross-linked by contacting theshunt with a solution of about 25% glutaraldehyde for a selected periodof time. One suitable form of glutaraldehyde is a grade 1G5882glutaraldehyde available from Sigma Aldridge Company of Germany,although other glutaraldehyde solutions may also be used. The pH of theglutaraldehyde solution should preferably be in the range of 7 to 7.8and, more preferably, 7.35-7.44 and typically about 7.4.+−.0.01. Ifnecessary, the pH may be adjusted by adding a suitable amount of a basesuch as sodium hydroxide as needed.

For example, a “permanent” implant can be crosslinked by keeping it in a25% Gluderaldehyde solution for 16 hours. This saturates thecrosslinking and results in a permanent implant that does not dissolveover any meaningful time frame (e.g., 10 years). However, in suchembodiments, a gelatin that has undergone much less crosslinking (usinga lower crosslinking time and/or a lower Gluderaldehyde concentration)can be used for the dissolvable section. By lowering the crosslinkingtime and/or the amount of Gluderaldehyde concentration, less thancomplete crosslinking can be achieved, which results in a dissolvingmaterial over an adjustable time frame. Other dissolvable materials andother crosslinking techniques can be used to provide the dissolvablesection.

According to some methods, by adjusting the Gluderaldehydeconcentration, crosslinking time, crosslinking temperature and/or thegeometry of the dissolvable section, the dissolving time can be from atleast about 15 minutes to several years. The dissolving time can also befrom at least about 1 hour to several months. For example, a completelynon-crosslinked gelatin dissolvable section can dissolve in about 20minutes. Therefore, the Gluderaldehyde concentration, crosslinking time,and/or the geometry (longitudinal length, aperture or channel size,etc.) of the dissolvable section can be modified accordingly to adjustthe dissolution rate of the dissolvable section.

Regarding the design considerations for shunt inner dimension ordiameter and length and dissolvable section length and channeldimensions, longer “pipes” have higher fluid resistance and fluidresistance decreases as “pipe” radius and cross-sectional area increase.Specifically, flow and resulting pressure values can be determined usingformulas known in the art. The flow rate for flow through a tube havingdifferent interior cross sections can be calculated using such formulas.Calculating laminar flow through a tube can be performed using theHagen-Poiseuille equation:

$\Phi = {\frac{\mathbb{d}V}{\mathbb{d}t} = {{v\;\pi\; R^{2}} = {{\frac{\pi\; R^{4}}{8\eta}\left( \frac{{- \Delta}\; P}{\Delta\; x} \right)} = {\frac{\pi\; R^{4}}{8\eta}\frac{{\Delta\; P}}{L}}}}}$

In the above formula, Φ is the volumetric flow rate, V is a volume ofthe liquid poured (cubic meters), t is the time (seconds), V is meanfluid velocity along the length of the tube (meters/second), x is adistance in direction of flow (meters), R is the internal radius of thetube (meters), ΔP is the pressure difference between the two ends(pascals), η is the dynamic fluid viscosity (pascal-second (Pa·s)), L isthe total length of the tube in the x direction (meters). Assuming thatthe flow restriction of a large lumen shunt is insignificant, thepressure difference ΔP between the shunt entrance and exit is given bythe length L and the inner diameter (radius R) of theplugged/constricted part of the shunt only.

Additionally, in accordance with some methods, the shunts of any ofFIGS. 3-23 may be made by dipping a core or substrate such as a wire ofa suitable diameter in a solution of material, such as gelatin. In somemethods, in order to form shunts having one or more restrictive sections(e.g., dissolvable portions), a core or substrate can be configured toinclude one or more peaks, valleys, protrusions, and/or indentationscorresponding to the desired inner profile of the shunt. The core orsubstrate can be coated or dipped multiple times in order to becomecoated with a desired number of layers or materials. For example, a coreor substrate can have a first section having a small outer diameter anda second section having a large outer diameter. The section having asmaller outer diameter can be coated or dipped in a solution such thatthe outer diameter along the first section is generally equal to thelarge outer diameter of the second section. Thereafter, the first andsecond sections of the core or substrate can be immersed in a solutionand dried. When removed, the shunt can therefore have an inner diameterthat narrows in a restricted section thereof, which corresponds to thefirst section of the core or substrate. Other details and features ofmethods of preparing and fabricating a shunt are disclosed in U.S.Application Publication Nos. 2012/0197175, filed on Dec. 8, 2011 andSer. No. 13/314,939, filed on Dec. 8, 2011, the entireties of each ofwhich are incorporated herein by reference.

In the case of a gelatin implant, the solution can be prepared bydissolving a gelatin powder in de-ionized water or sterile water forinjection and placing the dissolved gelatin in a water bath at atemperature of about 55° C. with thorough mixing to ensure completedissolution of the gelatin. In one embodiment, the ratio of solidgelatin to water is about 10% to 50% gelatin by weight to 50% to 90% byweight of water. In some embodiments, the gelatin solution includesabout 40% by weight, gelatin dissolved in water. The resulting gelatinsolution preferably is devoid of any air bubbles and has a viscositythat is from about 200 cp (centipoise) to about 500 cp. The solution canalso have a viscosity from about 260 to about 410 cp.

As discussed further herein, the gelatin solution may include biologics,pharmaceuticals, drugs, and/or other chemicals selected to regulate thebody's response to the implantation of the shunt and the subsequenthealing process. Examples of suitable agents include anti-mitolicpharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (suchas Lucintes, Macugen, Avastin, VEGF or steroids), anti-coagulants,anti-metabolites, angiogenesis inhibitors, or steroids. By including thebiologics, pharmaceuticals, drugs, or other chemicals in the liquidgelatin, the formed shunt will be impregnated with the biologics,pharmaceuticals, drugs, or other chemicals.

Drug-Eluting Shunts

In accordance with some embodiments, the shunt can comprise a drug ordrug-eluting portion for drug delivery to one or more target locationswithin the eye. A drug-eluting portion can be provided in combinationwith any of the embodiments disclosed or taught herein. For example,shunts such as those illustrated in FIG. 3-14 or 15-22 can comprise adrug-eluting portion. Thus, some embodiments provide a shunt that alsooperates as a drug delivery device inside the eye.

One or more drugs can be carried by the shunt for delivery to the targetlocation(s). The shunt itself can carry a drug and can be partially orcompletely dissolvable. For example, one or more drugs can be carried inone or more dissolvable coating(s) along a surface of the shunt. Thedrug-eluting dissolvable coating(s) can extend along the entire lengthor only a portion of the length of the shunt. The drug(s) can also becarried as a component of a dissolvable section, according to someembodiments. In some embodiments, a time controlled drug release can beachieved by configuring the dissolvable coating or portion to provide adesired dissolution rate. Such drug-eluting portion(s) of the shunt cantherefore provide a drug delivery, even without aqueous flow.

Aspects related to embodiments of drug delivery shunts are discussed inco-pending U.S. Application Publication No. 2012/0197175, filed on Dec.8, 2008, the entirety of which is incorporated herein by reference.

Various types of drugs can be used, including, glaucoma drugs, steroids,other anti-inflammatory, antibiotics, dry eye, allergy, conjunctivitis,etc.

At least a section of the shunt can comprise one or more drugs toprovide a drug-eluting portion. In some embodiments, one or more drugscan be provided along the entire length of the shunt. However, in someembodiments, one or more drugs can be provided along less than theentire shunt or along only a portion of the shunt. For example, a drugcan be integrated into only one of the ends of the shunt to provide asingle drug-eluting end which can be placed into the anterior chamber orlocation of lower pressure. Further, other than being formed along anend of the shunt, the drug-eluting portion can also be formed along anintermediate portion of the shunt. Accordingly, embodiments can providea targeted drug release inside the anterior chamber, inside the sclera,and/or in the subconjunctival space, depending on the location andconfiguration of the drug-eluting portion(s).

In some embodiments, the shunt can comprise multiple drug-elutingportions, which can each be formed to provide different dissolving timesand/or have different drugs embedded therein. Accordingly, in someembodiments, two or more drugs can be delivered simultaneously onindependent release timings.

For example, the shunt can comprise multiple dissolvable sections, whichcan each be formed to provide different dissolving times and/or havedifferent drugs embedded therein.

The shunt can also be implanted into the suprachoroidal space (which oneend in the anterior chamber and the other end in the suprachoroidalspace or with the entire shunt being completely suprachoroidal) with theability to deliver drugs at either or both ends or along an intermediateportion thereof. Some methods can be implemented such that multipleshunts (with the same or different drugs and with the same or differentrelease timings) can be implanted in different places (e.g., thesubconjunctival space, the suprachoroidal space, the anterior chamber,etc.).

For example, referring to FIG. 23, a shunt 700 can be implanted into aneye 702. The shunt 700 can extend not only within an anterior chamber704 of the eye 702, but also at least partially within the sclera 706and the subconjunctival space 708. Accordingly, the opportunity isprovided to configure the shunt 700 to comprise one or more drug-elutingportions to provide a targeted drug delivery to the anterior chamber704, the sclera 706, the subconjunctival space 708, and/or otherlocations in the eye 702.

In the illustrated embodiment, a dissolvable coating can be placed ontothe inner and/or outer surface of the shunt 700. Further, the shunt 700can comprise one or more dissolvable sections positioned within a lumenof the shunt. Thus, one or more drugs can be delivered to one or morelocations within the eye 702.

Tissue Compatible Shunts

In some embodiments, the shunt can comprise a material that has anelasticity modulus that is compatible with an elasticity modulus oftissue surrounding the shunt. For example, the intraocular shunt can beflexible, and have an elasticity modulus that is substantially identicalto the elasticity modulus of the surrounding tissue in the implant site.As such, embodiments of the intraocular shunt can be easily bendable,may not erode or cause a tissue reaction, and may not migrate onceimplanted.

Accordingly, when implanted in the eye using an ab intern procedure,such as some methods described herein, embodiments of the intraocularshunt may not induce substantial ocular inflammation such assubconjunctival blebbing or endophthalmitis. Additional exemplaryfeatures of embodiments of the intraocular shunt are discussed infurther detail below. In this manner, embodiments of the shunt can beconfigured to have a flexibility compatible with the surrounding tissue,allowing the shunt to remain in place after implantation without theneed for any type of anchor that interacts with the surrounding tissue.Consequently, some embodiments of the shunt can thereby maintain fluidflow away from an anterior chamber of the eye after implantation withoutcausing irritation or inflammation to the tissue surrounding the eye.

As discussed in applicant's co-pending application, U.S. applicationSer. No. 13/314,939, filed on Dec. 8, 2011, the entirety of which isincorporated herein by reference, elastic modulus or the modulus ofelasticity, is a mathematical description of an object or substance'stendency to be deformed elastically when a force is applied to it. Seealso Gere (Mechanics of Materials, 6th Edition, 2004, Thomson) (thecontent of which is incorporated by reference herein in its entirety).The elasticity modulus of a body tissue can be determined by one ofskill in the art. See, e.g., Samani et al. (Phys. Med. Biol. 48:2183,2003); Erkamp et al. (Measuring The Elastic Modulus Of Small TissueSamples, Biomedical Engineering Department and Electrical Engineeringand Computer Science Department University of Michigan Ann Arbor, Mich.48109-2125; and Institute of Mathematical Problems in Biology RussianAcademy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen etal. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996);Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No.96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol.16:241-246, 1990), the contents of each of which are incorporated byreference herein in its entirety.

The elasticity modulus of tissues of different organs is known in theart. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007)and Friberg (Experimental Eye Research, 473:429-436, 1988), bothincorporated by reference herein in their entirety, show the elasticitymodulus of the cornea and the sclera of the eye. Chen, Hall, and Parkershow the elasticity modulus of different muscles and the liver. Erkampshows the elasticity modulus of the kidney.

In some embodiments, the shunt can comprise a material that has anelasticity modulus that is compatible with the elasticity modulus oftissue in the eye, particularly scleral tissue. In certain embodiments,compatible materials are those materials that are softer than scleraltissue or marginally harder than scleral tissue, yet soft enough toprohibit shunt migration. The elasticity modulus for anterior scleraltissue is about 2.9±1.4×106 N/m2, and 1.8±1.1×106 N/m2 for posteriorscleral tissue. In some embodiments, the material can comprise agelatin. In some embodiments, the gelatin can comprise a cross-linkedgelatin derived from Bovine or Porcine Collagen. Further, the shunt cancomprise one or more biocompatible polymers, such as polycarbonate,polyethylene, polyethylene terephthalate, polyimide, polystyrene,polypropylene, poly(styrene-b-isobutylene-b-styrene), or siliconerubber.

Optional Shunt Features

As discussed in Applicant's co-pending application, U.S. applicationSer. No. 13/314,939, filed on Dec. 8, 2011, and in U.S. ApplicationPublication No. 2012/0197175, filed Dec. 8, 2011, the entireties of eachof which is incorporated herein by reference, some embodiments of theshunt can comprise optional features. For example, some embodiments cancomprise a flexible material that is reactive to pressure, i.e., thedimension or diameter of the flexible portion of the shunt fluctuatesdepending upon the pressures exerted on that portion of the shunt.Further, the shunt can comprise one or more side ports. Additionally,embodiments of the shunt can also comprise overflow ports. Someembodiments of the shunt can also comprise one or more prongs at an endthereof in order to facilitate conduction of fluid flow away from anorgan. In accordance with some embodiments, the shunt can also beconfigured such that an end of the shunt includes a longitudinal slit.Other variations and features of the shunt can be incorporated intoembodiments disclosed herein.

In addition to providing a safe and efficient way to relieve intraocularpressure in the eye, it has been observed that implanted shuntsdisclosed herein can also contribute to regulating the flow rate (due toresistance of the lymphatic outflow tract) and stimulate growth offunctional drainage structures between the eye and the lymphatic and/orvenous systems. These drainage structures evacuate fluid from thesubconjunctiva which also result in a low diffuse bleb, a small blebreservoir or no bleb whatsoever.

The formation of drainage pathways formed by and to the lymphatic systemand/or veins may have applications beyond the treatment of glaucoma.Thus, the methods of shunt implantation may be useful in the treatmentof other tissues and organs where drainage may be desired or required.

In addition, it has been observed that as a fully dissolvable shuntabsorbs, a “natural” microfistula shunt or pathway lined with cells isformed. This “natural” shunt is stable. The implanted shunt stays inplace (thereby keeping the opposing sides of the formed shunt separated)long enough to allow for a confluent covering of cells to form. Oncethese cells form, they are stable, thus eliminating the need for aforeign body to be placed in the formed space.

Deployment Devices

Deployment into the eye of an intraocular shunt according to thisdisclosure can be achieved using a hollow shaft configured to hold theshunt, as described herein. The hollow shaft can be coupled to adeployment device or part of the deployment device itself. Deploymentdevices that are suitable for deploying shunts according to theinvention include, but are not limited to the deployment devicesdescribed in U.S. Pat. Nos. 6,007,511, 6,544,249, and U.S. PublicationNo. US2008/0108933, the contents of each of which are incorporatedherein by reference in their entireties. In other embodiments, thedeployment devices can include devices such as those as described inco-pending and co-owned U.S. patent application Ser. No. 12/946,222,filed on Nov. 15, 2010, U.S. patent application Ser. No. 12/946,645,filed on Nov. 15, 2010, and co-pending U.S. application Ser. No.13/314,939, filed on Dec. 8, 2011, the contents of each of which areincorporated by reference herein in their entireties.

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the subject technology butmerely as illustrating different examples and aspects of the subjecttechnology. It should be appreciated that the scope of the subjecttechnology includes other embodiments not discussed in detail above.Various other modifications, changes and variations may be made in thearrangement, operation and details of the method and apparatus of thesubject technology disclosed herein without departing from the scope ofthe present disclosure. Unless otherwise expressed, reference to anelement in the singular is not intended to mean “one and only one”unless explicitly stated, but rather is meant to mean “one or more.” Inaddition, it is not necessary for a device or method to address everyproblem that is solvable by different embodiments of the disclosure inorder to be encompassed within the scope of the disclosure.

What is claimed is:
 1. A shunt for draining fluid from an anterior chamber of an eye, the shunt comprising: a main section having an inlet, an outlet, and wall defining a lumen with a first cross-sectional area and being configured to direct the fluid from the anterior chamber through the inlet toward the outlet such that, when positioned in the eye, fluid is released through the outlet at a location having lower pressure than the anterior chamber; a first detachable flow restriction section, positioned at the outlet, in fluid communication with the main section, the first detachable flow restriction section having a second cross-sectional area that is less that the first cross-sectional area; and a second, permanent, detachable flow restriction section, positioned at the inlet, in fluid communication with the main section, the second detachable flow restriction section having a third cross-sectional area that is less that the first cross-sectional area, the second detachable flow restriction section being severable to adjust a flow of fluid through the shunt.
 2. The shunt of claim 1, wherein the first cross-sectional area is generally circular in shape.
 3. The shunt of claim 1, wherein the first and second detachable flow restriction sections are each formed of a separate material from the main section.
 4. The shunt of claim 1, wherein the first detachable flow restriction section is dissolvable.
 5. The shunt of claim 4, wherein the first detachable flow restriction section has a dissolution rate that is different than a dissolution rate of the shunt.
 6. The shunt of claim 1, wherein the first detachable flow restriction section comprises first and second portions.
 7. The shunt of claim 6, wherein the first and second portions are axially spaced apart from each other.
 8. The shunt of claim 6, wherein the first and second portions are dissolvable.
 9. The shunt of claim 6, wherein the first and second portions are concentrically layered within the lumen.
 10. The shunt of claim 8, wherein the first portion has a first dissolution rate, and the second portion has a second dissolution rate different from the first dissolution rate.
 11. The shunt of claim 1, wherein at least a portion of the shunt comprises a drug.
 12. The shunt of claim 11, wherein the first or second detachable flow restriction section comprises a drug.
 13. The shunt of claim 1, wherein the first or second detachable flow restriction section comprises a gelatin.
 14. The shunt of claim 1, wherein the first detachable flow restriction section is permanent.
 15. The shunt of claim 1, wherein the second, permanent, detachable flow restriction section is nondissolvable in an eye over at least a ten year period.
 16. The shunt of claim 1, wherein the second, permanent, detachable flow restriction section comprises a cross-linked gelatin.
 17. The shunt of claim 16, wherein the second, permanent, detachable flow restriction section comprises a cross-linked gelatin subjected to a 25% Gluderaldehyde solution for 16hours.
 18. The shunt of claim 16, wherein the second, permanent, detachable flow restriction section comprises a cross-linked gelatin subjected to a crosslinker.
 19. The shunt of claim 18, wherein the crosslinker comprises a Gluderaldehyde solution.
 20. The shunt of claim 1, wherein the main section and the second, permanent, detachable flow restriction section comprise a cross-linked gelatin.
 21. An eye implant comprising a lumen, a first, permanent flow restrictor, and a second flow restrictor, the first and second flow restrictors being disposed within the lumen, the first flow restrictor positioned adjacent to an inlet of the implant, and the second flow restrictor positioned adjacent to an outlet of the implant, the implant being configured to conduct fluid at a first nonzero flow rate, modifiable to a second flow rate, when the implant is in an eye, by removing at least a portion of the first flow restrictor or the second flow restrictor, the implant configured to extend from the anterior chamber to a region of lower pressure.
 22. The implant of claim 21, wherein the implant comprises a wall defining the lumen, the wall having a variable inner profile.
 23. The implant of claim 21, wherein the first flow restrictor is nondissolvable in an eye over at least a ten year period.
 24. The implant of claim 21, wherein the second flow restrictor is permanent.
 25. The implant of claim 24, wherein the second flow restrictor is nondissolvable in an eye over at least a ten year period.
 26. The implant of claim 21, wherein the first flow restrictor comprises a cross-linked gelatin.
 27. The implant of claim 26, wherein the first flow restrictor comprises a cross-linked gelatin subjected to a crosslinker.
 28. The implant of claim 27, wherein the crosslinker comprises a Gluderaldehyde solution.
 29. The implant of claim 28, wherein the first flow restrictor comprises a cross-linked gelatin subjected to a 25% Gluderaldehyde solution for 16 hours.
 30. The implant of claim 21, wherein the second flow restrictor is dissolvable.
 31. The implant of claim 30, wherein the first nonzero flow rate is modifiable by dissolution of at least a portion of the second flow restrictor.
 32. The implant of claim 30, wherein the second flow restrictor comprises a drug.
 33. The implant of claim 21, wherein the second flow restrictor has a dissolution rate that is different than a dissolution rate of the shunt.
 34. The implant of claim 21, wherein the first and second flow restrictors each have lumens that define inner cross-sectional profiles that are less than an inner cross-sectional profile of the implant lumen. 